Computational methods: The geometry of a selected molecule was optimized to an rms (root mean square) gradient of 0.01 in vacuo (Polak-Ribire method). A periodic box, 15-15-15 around the drug was then set up, containing 112 water molecules. The system was optimized in MM+ using switched cut-offs (outer 10 and inner 14 ) to an rms gradient of 0.5. Then a molecular dynamics program was run for 1 ps, with 0.001 ps steps, relaxation time 0.1 ps, to a 30 simulation temperature of 300 K. This was followed by MM+ geometry optimization to an rms gradient of 0.2. The molecular dynamics run was repeated and a further MM+ protocol was carried out to a gradient of rms 0.2 on the selected drug. Finally, the geometries were optimized using the semiempirical AM1 programme in singly excited configuration interaction to a gradient of rms 0.01. (RHF [Restricted Hartree-Fock], charge 0, spin multiplicity 1, lowest state, orbital criterion, five occupied and five unoccupied orbitals.). Properties (c Log P, hydratation energies) were obtained from these semiempirical calculations with the QSAR package implemented in HyperChem Release 8.05 pro for Windows (Hypercube Inc. Gainesville, Florida.)
11
45149084105
J.-E. Rodriguez-Borges, S. Goncalves, M.L. Vale, X. Garcia-Mera, A. Coelho, and E. Sotelo J. Comb. Chem. 10 2008 372
Formation of azide was monitored by TLC. Trying to purify azides by chromatography did not improve yields of the following steps, and in addition some of them were obtained after with low yields purification (probably due to their degradation under the conditions of purification)
Formation of azide was monitored by TLC. Trying to purify azides by chromatography did not improve yields of the following steps, and in addition some of them were obtained after with low yields purification (probably due to their degradation under the conditions of purification).
20
0001698503
L.K. Dyall, G. L'abbé, and W. Dehaen J. Chem. Soc. 2 1997 971
